Hendrix was born in Oak Ridge, Tennessee, the daughter of Mary Elaine DePersio (1948–2017), of Italian, Irish and Danish descent, and Thomas Hendrix, Jr., a relative of John Hendrix (1865-1915). Her father was away from home serving in Vietnam at the time of her birth. A week after being born, with her mother considering the name Jennifer, Hendrix was instead named Katherine Elaine Hendrix. Most of her relatives called her by her middle name, and the practice stuck, but it forced Hendrix many times to explain the middle name. She has a brother, David Maher, and a sister, Stephanie Smith; both are married and have children. Hendrix was raised in Morristown, Tennessee. When Hendrix was 15, she and her mother moved to Atlanta, Georgia, where she attended the Northside School of Performing Arts. Hendrix currently resides in Los Angeles. She is regularly involved with humanitarian efforts.
In her senior year of high school Hendrix won a model search and became a professional dancer with the Gary Harrison Dance Co. She soon split her time as a professional model and dancer for such companies as Nike, Levi's, Mattel, and Sun Microsystems, and for a number of hip-hop artists including Whodini, Keith Sweat, and MC Hammer.
In 1992 she moved to Los Angeles, California, and shortly after moving was hit by a car while riding her bike, ending her early career as a model and dancer.
After recuperating from her accident, Hendrix was cast in the short-lived 1995 Get Smart series. She has also appeared on the television series Joan of Arcadia, Friends, Ellen, Charmed and CSI: Crime Scene Investigation and had a recurring role in Married... with Children, User Friendly (1995) and Lez Be Friends (1997). Films in which she appeared include Romy and Michele's High School Reunion, the remake of The Parent Trap, Superstar, the movie version of Inspector Gadget — Inspector Gadget 2, and What the Bleep Do We Know!?. In 2006, she also appeared in an episode of Ghost Whisperer and the movie Coffee Date. In 2008 Hendrix appeared in two episodes of the now cancelled ABC Family show The Middleman as Roxy Wasserman, a succubus who works as a fashion designer.
She was seen in "Criminal Minds" in season four, episode 11 ("Normal", 2008) where she played a woman called Judy Hannity in a car accident caused by a man shooting her, but she survived. In 2009 Hendrix made an appearance on the ABC show Castle and in the film Rock Slyde (2009 Film).
In 2010 Hendrix played Felicia in the TriBeCa awarded film Spork.
Hendrix has also appeared as Renee on 90210 in Season 3 in "They're Playing Her Song" and "Holiday Madness". In 2014, she appeared alongside Charlie Sheen for a three-episode story arc as Warden Hartley in the FX sitcom Anger Management.
She can currently be seen in the web-series Fetching, which is also a nod to her love of animals.
She also co-starred as Ava in the FX comedy series Sex&Drugs&Rock&Roll with Denis Leary, Elizabeth Gillies, John Corbett, Bobby Kelly and John Ales.
As an avid animal rights activist, Hendrix has been advocating for animals since 2006. When she's not filming, she travels throughout North America and works with organizations around the globe to educate, demonstrate, speak, protest, build habitats, transport and rescue. In 2012 she founded The Pet Matchmaker, an organization dedicated to celebrating and inspiring the rescue, foster and adoption of homeless pets everywhere. She serves on the board of Stray Rescue of St. Louis as well as the US chapter of No to Dog Meat.